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Aging may be reversed by smoothing out the wrinkles in our...cells

Healthline/Medical News Today Jun 01, 2018

Why do we age, and why do we tend to become more ill as we do so? Most importantly, what can we do to stop this imminent process? New research might have found the answer to such questions, and it lies in our wrinkles—not the ones lining our faces, but the ones in our cells.

Over recent years, more and more research has been zeroing in on the aging process and what we can do to stop it—and understandably so.

Seniority may come with a range of conditions, including diabetes, fatty liver disease, cancer, cardiovascular disease, and even some neurodegenerative conditions, such as Alzheimer's.

But what is the underlying cause of these aging-associated illnesses? Homing in on what occurs during aging on a cellular level may hold the answer.

From rejuvenating existing cells to simply adding fresh stem cells to replace old ones, scientists are trialing a variety of approaches that could extend our lives and keep us disease-free for longer.

Now, a team of researchers—led by Irina M. Bochkis, PhD, of the University of Virginia School of Medicine in Charlottesville—has made a fascinating discovery. The nuclei inside our cells, they show, tend to "wrinkle" as we age.

These wrinkles impair the functioning of our genes, report the scientists. Luckily, however, Bochkis and her team also have a few ideas about how to stop—or maybe even reverse—the aging process by "smoothing out" these wrinkles.

The results of this innovative study were published in the journal Aging Cell.

How cellular wrinkles cause disease

The nucleus of a cell stores our DNA, explain the authors, and the new study shows the location of our DNA within the nucleus to be of crucial importance.

"We have the same DNA in every single cell, but each cell is different," explains Bochkis. "So how does that work?"

"Well, actually, certain genes need to be on in the liver, and they have to be turned off in the brain, for example, and vice versa," she adds. "If they're not turned off appropriately, then you have problems."

Normally, when these genes are turned off, they are then pushed up against the membrane that envelops the nucleus. But, with age, this nuclear membrane becomes lumpy and wrinkly, which stops the genes from switching off as they should.

Turning to the example of fatty liver disease—a condition tied to the aging process, which Bochkis and her colleagues have taken as a model in their study—the senior investigator explains, "When your nuclear membrane is no longer functioning properly, it can release the DNA that's supposed to be turned off."

"So then your little liver cell becomes a little fat cell," she continues, adding that this important organ "can end up looking like Swiss cheese."

Is there a 'face cream' for our cells?

Similarly to how facial wrinkles are due to a lack of collagen, cellular wrinkles are caused by a lack of a substance called lamin. Lamins are a family of proteins that provide the cell with stability and strength.

The National Institutes of Health (NIH) say that lamins are "supporting (scaffolding) components of the nuclear envelope." They are located "in the nuclear lamina, a mesh-like layer of intermediate filaments and other proteins that is attached to the inner membrane of the nuclear envelope."

The nuclear envelope, or membrane, controls what molecules go in and out of the nuclear cell; by replacing the lost lamin, say the authors of the new study, we should be able to smooth out the wrinkles of the nuclear membrane.

So how could we "deliver" this vital protein at such a microscopic level to the nuclear membrane of the cell? Bochkis believes that modified viruses could work perfectly as a viable means of "transporting" the lamin "cargo."

In gene therapy, engineered viruses are already being used as "vectors" to deliver new genes by infecting the cells.

If the approach of using viruses proves successful, "You're going to have [...] normal, healthy cells—and they will appropriately express the genes that should be expressed," explains Bochkis.

Such youthful cells would help to keep a range of aging-related cardiometabolic conditions, such as diabetes and heart disease, at bay.

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